Degeneration of tissues such as cartilage is a common health condition that has a significant economic impact and quality of life impact. For example, osteoarthritis (OA) and other rheumatic diseases are among the most common health conditions and are the number one cause of disability in the United States, affecting an estimated 27 million Americans in 2008 (Lawrence et al. (2008). Arthritis Rheum. 58, pp. 26-35). The economic impact of arthritis in the United States is estimated at $128 billion per year, representing more than 2% of the gross domestic product ((CDC), C.f.D.C.a.P. MMWR Morb Mortal Wkly Rep. 56, 4-7 (2007)). Only symptom-modifying therapies are used to treat OA (Roddy et al. (2005). Rheumatology (Oxford, England) 44, pp. 67-73; Zhang et al. (2005). Annals of the rheumatic diseases 64, pp. 669-681).
For two decades, one major cell-based tissue regeneration strategy—autologous cell implantation, has been clinically approved. However, this procedure does not predictably result in functional hyaline cartilage, but rather in fibrocartilage (Roberts et al. (2009). Knee 16, pp. 398-404; Zeifang et al. Am. J. Sports Med. 38, pp. 924-933), which lacks the cellular and extra-cellular matrix (ECM) organization required to support the demanding load-bearing functions of this tissue (Lee et al. (2007). Biomaterials 28, pp. 2987-2993; Klein et al. (2009). Tissue Eng. Part B Rev. 15, pp. 143-157).
Although in vitro prefabrication of tissue grafts has shown variable success in animal models and cartilage tissues engineered with zonal organization has improved to provide a natural spatial cell distribution, these approaches have not been transferred to a clinical setting (Chu et al. (2010). Tissue Eng. Part B Rev. 16, pp. 105-115; Kim et al. (2003). Osteoarthritis Cartilage 11, pp. 653-664; Klein et al. (2009). Tissue Eng. Part B Rev. 15, pp. 143-157; Klein et al. (2003). Osteoarthritis Cartilage 11, pp. 595-602; Sharma et al. (2007). Tissue Eng. 13, pp. 405-414; Woodfield et al. (2004). Biomaterials 25, pp. 4149-4161). The procedures are laborious, expensive and integration into the surrounding host cartilage tissue is an unresolved issue (Obradovic et al. (2001). J. Orthop. Res. 19, pp. 1089-1097).
Accordingly, there is a need for improved methods of tissue engineering, particularly for tissues such as cartilage. The methods of the present invention provide such improved methods.